Genetic Variant NM_001080471.3:c.1952-80C>T (chr1-156912167-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080471.3(PEAR1):c.1952-80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,520,274 control chromosomes in the GnomAD database, including 11,922 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1401 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10521 hom. )

Consequence

PEAR1
NM_001080471.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Publications

22 publications found

Variant links:

Genes affected

PEAR1 (HGNC:33631): (platelet endothelial aggregation receptor 1) PEAR1 is a platelet receptor that signals upon the formation of platelet-platelet contacts independent of platelet activation and secondary to platelet aggregation (Nanda et al., 2005 [PubMed 15851471]).[supplied by OMIM, Mar 2008]

PEAR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080471.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PEAR1	NM_001080471.3	MANE Select	c.1952-80C>T	intron	N/A	NP_001073940.1
PEAR1	NM_001353682.2		c.1760-80C>T	intron	N/A	NP_001340611.1
PEAR1	NM_001353683.2		c.1760-80C>T	intron	N/A	NP_001340612.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PEAR1	ENST00000292357.8	TSL:5 MANE Select	c.1952-80C>T	intron	N/A	ENSP00000292357.7
PEAR1	ENST00000338302.7	TSL:5	c.1952-80C>T	intron	N/A	ENSP00000344465.3
PEAR1	ENST00000469390.5	TSL:2	n.1680-80C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19760

AN:

152004

Hom.:

1395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.114

AC:

155321

AN:

1368152

Hom.:

10521

AF XY:

0.115

AC XY:

77443

AN XY:

672932

show subpopulations

African (AFR)

AF:

0.145

AC:

4442

AN:

30588

American (AMR)

AF:

0.106

AC:

3412

AN:

32158

Ashkenazi Jewish (ASJ)

AF:

0.0996

AC:

2072

AN:

20798

East Asian (EAS)

AF:

0.353

AC:

13611

AN:

38576

South Asian (SAS)

AF:

0.162

AC:

11561

AN:

71290

European-Finnish (FIN)

AF:

0.139

AC:

6707

AN:

48280

Middle Eastern (MID)

AF:

0.110

AC:

455

AN:

4148

European-Non Finnish (NFE)

AF:

0.0995

AC:

106059

AN:

1065870

Other (OTH)

AF:

0.124

AC:

7002

AN:

56444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6586

13172

19758

26344

32930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4150

8300

12450

16600

20750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19775

AN:

152122

Hom.:

1401

Cov.:

AF XY:

0.134

AC XY:

9959

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.142

AC:

5888

AN:

41514

American (AMR)

AF:

0.123

AC:

1882

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

363

AN:

3472

East Asian (EAS)

AF:

0.332

AC:

1712

AN:

5154

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4824

European-Finnish (FIN)

AF:

0.139

AC:

1476

AN:

10582

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7183

AN:

67980

Other (OTH)

AF:

0.132

AC:

279

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

875

1750

2624

3499

4374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

2078

Bravo

AF:

0.130

Asia WGS

AF:

0.245

AC:

850

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.0

(source)

DANN

Benign

0.51

PhyloP100

0.061

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over